Variant 3-14505689-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001080423.4(GRIP2):c.2499G>A(p.Thr833=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000748 in 1,603,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

GRIP2
NM_001080423.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.45

Variant links:

Genes affected

GRIP2 (HGNC:23841): (glutamate receptor interacting protein 2) Predicted to enable protein C-terminus binding activity. Predicted to be involved in several processes, including neurotransmitter receptor transport, endosome to postsynaptic membrane; positive regulation of AMPA glutamate receptor clustering; and positive regulation of excitatory postsynaptic potential. Predicted to act upstream of or within Notch signaling pathway; artery smooth muscle contraction; and positive regulation of blood pressure. Predicted to be located in cytoplasm; dendritic shaft; and neuron spine. Predicted to be active in glutamatergic synapse and postsynaptic density. [provided by Alliance of Genome Resources, Apr 2022]

GRIP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 3-14505689-C-T is Benign according to our data. Variant chr3-14505689-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653582.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.45 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIP2	NM_001080423.4 linkuse as main transcript	c.2499G>A	p.Thr833=	synonymous_variant	20/24	ENST00000621039.5	NP_001073892.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIP2	ENST00000621039.5 linkuse as main transcript	c.2499G>A	p.Thr833=	synonymous_variant	20/24	1	NM_001080423.4	ENSP00000478352	P2	Q9C0E4-1
GRIP2	ENST00000619221.4 linkuse as main transcript	c.2790G>A	p.Thr930=	synonymous_variant	21/25	5		ENSP00000480660
GRIP2	ENST00000637182.1 linkuse as main transcript	c.2514G>A	p.Thr838=	synonymous_variant	20/24	5		ENSP00000490949	A1
GRIP2	ENST00000430219.2 linkuse as main transcript	c.876G>A	p.Thr292=	synonymous_variant, NMD_transcript_variant	8/12	2		ENSP00000481670

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000309

AC:

AN:

226680

Hom.:

AF XY:

0.0000406

AC XY:

AN XY:

123038

show subpopulations

Gnomad AFR exome

AF:

0.0000747

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000601

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000497

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000758

AC:

AN:

1451178

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

720804

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000903

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

GRIP2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.2

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over